Seven laboratories in the Departments of Medicine, Genetics, Pathology, Medical Microbiology and Biological Sciences will pursue an analysis of the molecular genetics, expression, regulation and function of a variety of specific proteins and polypeptides which are selectively expressed in functionally distinct lymphocyte and macrophage subsets, and which are required for the function of these differentiated cell types. The overall purpose of the program project is to identify the major gene products involved in differentiated lymphocyte function and to understand the molecular basis of T cell antigen recognition, the molecular differences between helper and suppressor T cell subsets, the molecular basis of T cell-macrophage and T cell-B-cell interaction, the molecular basis of lymphocyte homing and the function of specific receptors on activated lymphocytes, as well as the mechanisms regulating Ig class switching in B lymphocytes and Ia expression during B cell development. Cloned T cell lines, molecular cloning of B cell, T cell, and macrophage gene products, synthetic oligonucleotide probes, and synthetic peptide antigens will be used to isolate cDNA and genomic clones encoding molecules uniquely expressed in T lymphocytes, B lymphocytes, and antigen presenting cells. cDNA and genomic clones will be used for studies of regulation of expression of these gene products, for probing the mechanism of interactions between various gene products, and for transfecting cell lines and zygotes to permit structure-function analysis of the mechanism of action of gene products which mediate specific differentiated lymphocyte functions.